House R V, Thomas P T, Bhargava H N
Life Sciences Department, IIT Research Institute, Chicago, IL 60616, USA.
Neuropeptides. 1997 Feb;31(1):89-93. doi: 10.1016/s0143-4179(97)90026-3.
Previous studies by our group have demonstrated that in vitro exposure to delta-opioid receptor agonists results in a significant immunostimulation, whereas in vitro exposure to non-peptidic delta-opioid receptor antagonists results in significant suppression of various immune functions. The present study assessed potential immunomodulation by the peptidic delta-opioid receptor antagonists TIPP, D-TIPP, and ICI 174864 using a panel of in vitro immune function assays. Splenocytes from female B6C3F1 mice were cultured with the peptides at concentrations of 0.00001-10 microM. B cell proliferation was quantified following cellular activation, T cell function was assessed by cytokine production following stimulation with anti-CD3 monoclonal antibody, natural immunity was assessed by quantitating natural killer (NK) cell activity following a 24-h exposure, and macrophage function was assessed by quantification of interleukin-6 (IL-6) production. None of the peptides examined significantly affected B cell proliferation. Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-TIPP, but was significantly suppressed at 10 microM ICI 174864. Production of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI 174864. IL-6 production by macrophages was unaffected except for sporadic incidents of enhanced production in cells exposed to ICI 174864. NK cell function exhibited a differential pattern of suppression, with the greatest degree of suppression observed following exposure to TIPP and only slight suppression in cells exposed to either D-TIPP or ICI 174864. These data suggest that peptidic delta-opioid receptor antagonists do not exhibit the same pattern or degree of immunosuppressive activity as the non-peptidic antagonists at equivalent in vitro concentrations.
我们团队之前的研究表明，体外暴露于δ-阿片受体激动剂会导致显著的免疫刺激，而体外暴露于非肽类δ-阿片受体拮抗剂会导致各种免疫功能受到显著抑制。本研究使用一系列体外免疫功能测定方法，评估了肽类δ-阿片受体拮抗剂TIPP、D-TIPP和ICI 174864的潜在免疫调节作用。将雌性B6C3F1小鼠的脾细胞与浓度为0.00001 - 10 microM的肽一起培养。细胞活化后对B细胞增殖进行定量，用抗CD3单克隆抗体刺激后通过细胞因子产生评估T细胞功能，24小时暴露后通过定量自然杀伤（NK）细胞活性评估天然免疫，通过定量白细胞介素-6（IL-6）产生评估巨噬细胞功能。所检测的肽均未显著影响B细胞增殖。TIPP或D-TIPP暴露对T细胞产生IL-2的影响并不一致，但在10 microM ICI 174864时受到显著抑制。然而，低浓度的TIPP或D-TIPP以及10 microM ICI 174864均显著抑制IL-4的产生。巨噬细胞产生IL-6未受影响，除了在暴露于ICI 174864的细胞中偶尔出现产生增强的情况。NK细胞功能呈现出不同的抑制模式，暴露于TIPP后观察到最大程度的抑制，而暴露于D-TIPP或ICI 174864的细胞中仅有轻微抑制。这些数据表明，在等效的体外浓度下，肽类δ-阿片受体拮抗剂与非肽类拮抗剂相比，不表现出相同模式或程度的免疫抑制活性。
